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Biomedical subjects

J Kutti

Publications and source records attributed to J Kutti.

At least 55 records · Page 3Linked to original sources
PubMed1995

Glycoprotein IIb/IIIa autoantigenic repertoire in chronic idiopathic thrombocytopenic purpura.

The objective of the present study was to further disclose the autoantigenic repertoire carried by the platelet glycoprotein (GP) IIb/IIIa complex. IgG-F(ab')2 fragments were prepared from two prototype ITP patients, and their ability to block the binding of GPIIb/IIIa reactive antibodies derived from other patients with ITP was evaluated using a modified MAIPA asay; a PlA1 alloantiserum and 20 normal sera were included as controls. It was found that the two prototype IgG-F(ab')2 fragments were each able to significantly block the binding of serum IgG to GPIIb/IIa in six (55%) and seven (64%) out of 11 patients with chronic ITP, respectively. No significant blocking effect was observed for IgG-F(ab')2 fragments prepared from normal subjects. Also, the binding of the PlA1 alloantiserum to its epitope on GPIIIa was not affected by any of the blocking IgG-F(ab')2 fragments exploited in the study. These data substantiate that in chronic ITP at least half of the GPIIb/IIIa reactive sera bind to homogenous autoepitopes.

Adolescent↗
PubMed1995

Effects of Erwinia-asparaginase on the coagulation system.

L-Asparaginase treatment during induction therapy in acute lymphoblastic leukaemia (ALL) is known to be frequently complicated by thromboembolic events. It was recently suggested that L-asparaginase derived from Erwinia chrysanthemi alters the coagulation system less severely than does Escherichia coli asparaginase. In a series of 11 adult patients with ALL, we investigated some parameters of the coagulation system during treatment with Erwinia asparaginase. The doses employed were rather high; all patients below the age of 60 years received 15,000 U/m2 daily over 14 days. In accordance with what is known from treatment with E. coli asparaginase, we observed significant lowering of antithrombin as well as of fibrinogen. However, as to fibrinogen indeed a significant decrease had occurred prior to the institution of Erwinia asparaginase treatment. The most striking observation in the present study was that the levels of prothrombin complex, reflecting the function of K-vitamin dependent coagulation factors II, VII and X, remained within normal ranges during treatment. This indicates that these coagulation factors were not affected by Erwinia asparaginase, an observation at variance with several reports where E. coli asparaginase was investigated. This latter observation was the only finding which could lend support to the view that Erwinia asparaginase affects the coagulation system less than E. coli asparaginase. Finally, one of our patients developed a sinus thrombosis, a severe thrombotic complication.

Adolescent↗
PubMed1995

Antibodies against platelet GPIb/IX, GPIIb/IIIa, and other platelet antigens in chronic idiopathic thrombocytopenic purpura.

Antibodies involved in the pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP) react most frequently with platelet glycoprotein (GP) Ib/IX and GPIIb/IIIa. However, uncertainty as to the specificity, frequency, and clinical significance of such antibodies still remains. By using a modified antigen-capture ELISA (MACE), an immunoprecipitation assay, and an immunoblot assay, sera from 60 patients with chronic ITP were analyzed. GP-specific antibodies were found in 50% (30/60) of the patients, with 14 patients having antibodies directed solely to GPIIb/IIIa, 8 holding antibodies specific only for GPIb/IX, and 8 possessing antibodies against both antigens. Serum antibodies were more frequently (p < 0.01) detected in either active and/or non-splenectomized ITP patients. Moreover, in patients displaying antibodies against GPIb/IX, significantly (p < 0.05) lower platelet counts were observed. Using the immunoblot assay, antibodies specific for a 30 kD platelet antigen were detected in 12 of 60 patients. This antigen could not be immunoprecipitated from surface labelled platelet membranes, indicating an intracellular location. We conclude that in chronic ITP, (1) the frequency of anti-GPIIb/IIIa antibodies is close to that of anti-GPIb/IX antibodies, (2) anti-GP antibodies are more likely to be detected in patients with an active disease status and, (3) a 30 kD internal platelet protein is another frequent antigen.

Adult↗
PubMed1994

Peripheral and intrasplenic platelet kinetics and bone marrow megakaryopoiesis in alpha-2b-interferon treated hairy cell leukemia.

In eight patients with previously untreated hairy cell leukemia (HCL), by using 111In-labelled platelets and megakaryocyte quantitation, the splenic platelet pooling and the platelet production rate (P) were evaluated before and during alpha-2b-interferon (IFN) treatment. Both before and after 8 months of IFN therapy the spleen was shown to pool a sizeable amount of the total body platelet mass. The average splenic platelet pools, prior to and after 8 months of IFN, were 58 +/- 17 and 47 +/- 11%, respectively. At the time when treatment was initiated, the patients were heterogeneous as regards the spleen size, platelet kinetics, and the bone marrow morphology. Three patients had values for P below the 95th percentile for a group of healthy control subjects; following IFN therapy they displayed a substantial increase in P. In three other HCL patients, with the largest spleens, the pre-treatment P was normal, or slightly above the values seen for the control subjects. In these patients, changes in splenic platelet pool size, blood volume, and platelet mean life-span accounted for the increase in platelet count observed in response to IFN. The mean megakaryocyte number and volume per microliter bone marrow increased during IFN therapy, while the mean P remained slightly reduced. It is concluded that splenic platelet pooling would explain the previously described difference in platelet counts between splenectomized and non-splenectomized patients treated with IFN.

Adult↗
PubMed1994

Hormone conference at Sahlgren's University Hospital: polycythemia and inappropriately high serum erythropoietin concentration in a 62-year-old man.

A 62-year-old man with a history of coronary insufficiency complained at his scheduled visit to the outpatient clinic of symptoms suggestive of gastritis. His blood hemoglobin concentration, however, was markedly increased. Results of a hematological work-up suggested an erythropoietin-producing tumor. Signs of increased intracranial pressure then led to the finding of a cerebellar tumor, which could explain his vertigo and abdominal symptoms. This cystic capillary hemangioblastoma probably was responsible for the erythropoietin production and also seemed to produce basic fibroblast growth factor. The clinical evaluation of polycythemia as well as erythropoietin biochemistry and clinical application are reviewed.

Capillaries↗
PubMed1993

Some relations between light transmission changes and biochemical parameters of stored platelet packs.

In the present work a computerised method for continuous monitoring of light transmission through platelet packs was evaluated. On series (Series 1) of 50 platelet concentrates was studied over a 5-day period, and thereafter the pH, extracellular lactate dehydrogenase (LDH) and platelet factor 4 (PF4) in the concentrates were determined. A second series (Series 2) of 52 concentrates was also monitored over 5 days, and thereafter the pH, extracellular LDH and intracellular concentrations of ATP, ADP and AMP were determined. 11 and 14 of the concentrates of Series 1 and 2, respectively, demonstrated long lasting transmission increases (> or = 3.0 days). In the total of 102 platelet concentrates 34 were observed to have late (< 1.0 day) or no transmission increase. It is concluded, that the present optical method identifies both a group of platelet concentrates having long lasting transmission increases and a group consisting of platelet concentrates having late or no transmission increase. Compared to the latter concentrates preparations with long lasting transmission changes demonstrated significant biochemical alterations. These observations could be applicable in the quality control of platelet concentrates.

Adenosine Diphosphate↗
PubMed1993

Measurement of spleen size using gamma camera scintigraphy in essential thrombocythaemia.

By using gamma camera imaging the spleen size was determined in 33 consecutive patients with essential thrombocythaemia (ET) and in 33 consecutive patients with reactive thrombocytosis (RT). All ET patients were newly diagnosed and had not received myelosuppressive treatment prior to study; they all fulfilled the criteria for ET as established by the Polycythemia Vera Study Group. In both posterior and lateral projections, the spleen area in the group of ET patients was significantly larger than in the RT patients. The present study has shown that 39% of ET patients at diagnosis have splenic enlargement. Evaluation of spleen size is therefore a useful diagnostic test in patients presenting with unexplained thrombocytosis.

Adult↗
PubMed1992

Cigarette smoking increases thromboxane A2 formation without affecting platelet survival in young healthy females.

Smoking is a risk factor for the development of atherosclerotic cardiovascular disease, in men as well as in women. An increased urinary excretion of the thromboxane metabolite 2,3-dinorthromboxane B2 (Tx-M) has been observed in smokers of both genders, suggesting that cigarette smoking may facilitate cardiovascular disease via an action on the platelets. The present study addressed the hypothesis that the increased Tx-M excretion in female smokers reflects a true facilitation of platelet reactivity in vivo, rather than an increased destruction of the platelets. In healthy female volunteers (aged 20-46 years, 18 smokers and 17 non-smokers) platelet life-span and indices of platelet activity were determined, together with plasma levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen, peripheral blood cell counts and hematocrit. The urinary excretion of Tx-M was higher in smokers than in non-smokers (361 vs. 204 pg/mg creatinine, respectively, p < 0.05), while plasma and urinary beta-thromboglobulin, plasma platelet factor 4, platelet mean life-span and platelet production rate did not differ between the groups. PAI-1 activity, white blood cell count and hematocrit were higher in smokers than in non-smokers (p < 0.05). These data indicate that smoking facilitates platelet formation of thromboxane A2 without affecting platelet survival; i.e. it increases the activity of platelets without affecting their viability to a measurable extent. Such an increase in platelet activity, operating in parallel to a reduced fibrinolytic activity and a higher hematocrit and white blood cell count, may play an etiological role in smoking-induced cardiovascular disease in women.

Adult↗
PubMed1992

Some storage characteristics of buffy coats used for preparation of platelet concentrates.

The present study examined biochemical storage lesions in 58 buffy coats (BCs) intended as the raw material for platelet concentrates. The work was conducted in three series; the aims were to investigate: (a) the storage quality of BCs obtained from the routine production (series I), (b) whether improvement in platelet quality could be achieved by continuous agitation during storage (series II), and (c) whether macroscopic aggregate formation indicates platelet damage (series III). Series I and II consisted of 20 BCs each. Series III compared ten BCs with visible clumping with eight BCs not demonstrating macroscopic aggregates. In series I and II platelet counts and platelet factor 4 (PF4) release were determined after 1, 3, 5, and 24 h; lactate dehydrogenase (LDH) extracellular activity was measured after 1 and 24 h. In addition, in series I elastase concentrations were analyzed after 3, 5, and 24 h. Finally, in series III extracellular beta-thromboglobulin (beta-TG) levels were determined after 18-24 h. Low platelet counts, most likely reflecting the presence of aggregate formation, were found in 20% of the BCs (series I); in this series a total of 25% demonstrated increasing platelet counts, together with elevated PF4 and elastase, over the study period. Significant biochemical storage lesions were found after 5 and 24 h of storage. The study also demonstrated that continuous agitation during storage does not improve platelet quality (series II) and that BCs demonstrating visible clumping (series III) had augmented levels of extracellular beta-TG (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1992

Dysplastic megakaryopoiesis with thrombocytopenia and chromosomal aberration.

A case of isolated thrombocytopenia with decreased platelet production and abnormal megakaryopoiesis is described. In the bone marrow, a chromosomally aberrant clone, 45,XX,-11,-18,+der (11;18)(11q13;18p11), was found. These findings indicate a myelodysplastic nature of the abnormal thrombocytopoiesis. The described case demonstrates the value of a bone marrow examination including histopathology with immunologic techniques to evaluate the megakaryopoiesis in thrombocytopenia and the interest of cytogenetic studies not only in instances with overt hematologic malignancies or complete myelodysplastic syndromes, but also when morphologic abnormalities occur in a single cell line.

Biopsy↗
PubMed1992

Investigation of how different filters affect some biochemical properties of stored platelet concentrates.

The aim of the present study was to investigate how four different filters, i.e. Imugard IG500 (Terumo, Japan), Miropore (Miramed, Italy), Pall P1-100 (Pall, USA) and Sepacell P1-10A (Asahi, Japan) affect some biochemical properties of platelet concentrates. The work was conducted using 42 pairs of platelet concentrates. After 2 days of storage, one of the preparations was filtered and the other served as an unfiltered control. Immediately after filtration, determination of the platelet count, desarginated activated complement factor 3 (C3a des arg) and the extracellular and total concentrations of platelet factor 4 (PF4) and lactate dehydrogenase (LDH) were carried out on both these platelet concentrates. After an additional storage period of 3 d, extracellular concentrations of PF4 and LDH were determined on both concentrates. A significant decrease of extracellular PF4 concentration was found immediately after filtration when Pall P1-100 and Imugard IG500 were used. During the 3-d storage after filtration, the concentrates filtered with Imugard IG500 and Pall P1-100 demonstrated significantly higher platelet lysis as compared to the unfiltered controls. It is concluded that the present work demonstrates storage instability after filtration with Imugard IG500 and Pall P1-100. Therefore, platelet concentrates filtered with these filters would not appear to be suitable for storage.

Blood Platelets↗
PubMed1991

The effect of alpha-interferon on bone marrow megakaryocytes and platelet production rate in essential thrombocythemia.

In 10 patients with previously untreated essential thrombocythemia (ET), by using 111In-labeled platelets and megakaryocyte morphometry, the relation between platelet production rate and bone marrow megakaryocytes was evaluated before and during alpha-2b-interferon (IFN) therapy. A highly significant decrease in platelet count occurred during IFN therapy; the platelet counts, at baseline and after 2 and 6 months of IFN therapy, were 1,102 +/- 345 x 10(9)/L, 524 +/- 169 x 10(9)/L (P less than .0001), and 476 +/- 139 x 10(9)/L (P less than .0001), respectively. The decrement in platelet count was mainly a result of diminished platelet production rate, which at baseline and after 2 and 6 months of IFN therapy was 89 +/- 30 x 10(10) platelets/d, 53 +/- 18 x 10(10) platelets/d (P = .0033), and 45 +/- 20 x 10(10) platelets/d (P less than .0001), respectively. Also, a slight shortening of platelet mean life-span (MLS) was observed in response to IFN treatment; platelet MLS was 7.96 +/- 0.69 days at baseline and 6.68 +/- 1.30 days (P = .012) after 6 months of IFN therapy. IFN induced a significant decrease in bone marrow megakaryocyte volume; both megakaryocyte nuclear and cytoplasmatic volumes were affected. The mean megakaryocyte volume was 372 +/- 126 x 10(2) pL/microL at baseline and 278 +/- 147 x 10(2) pL/microL (P = .049) after 6 months of IFN therapy. However, the number of megakaryocytes did not show any significant change in response to IFN. It is concluded that alpha-IFN reduces platelet production rate and the peripheral platelet count in ET mainly through an anti-proliferative action on the megakaryocytes and to a considerably lesser degree by a shortening of platelet MLS.

Adult↗
PubMed1991

The in vivo kinetics of 111In- and 51Cr-labelled platelets: a comparative study using both stored and fresh platelets.

The in vivo kinetics of simultaneously injected 51Cr- and 111In-labelled platelets was investigated in 20 healthy male volunteers. The studies were carried out using both fresh platelets and platelets stored for 5 d at 22 degrees C; the disappearance of platelet-bound radioactivity was measured on whole blood samples as well as platelet pellets. Compared to 111In, the labelling efficiency was notably lower for 51Cr, and a higher amount of 51Cr was bound to contaminating red cells. As regards the fresh platelets, only small dissimilarities were observed in the in vivo kinetics obtained with the two labels. 51Cr yielded a slightly higher platelet recovery and longer T1/2 than 111In, when whole blood samples were used for calculations; no differences were seen when using platelet pellets. When stored platelets were studied, 51Cr gave significantly longer T1/2 and mean life-span (MLS) than did 111In. This difference was present for all mathematical models used for the calculation of MLS, and when whole blood samples as well as platelet pellets were employed. It was demonstrated that the estimation of MLS was also highly dependent upon techniques of blood sampling and curve fitting. Calculation, in which the initial data points were excluded, gave consistently longer MLS (P less than 0.0001), as compared to when all data points were included. Furthermore, when all survival studies were grouped together, calculations using platelet pellets gave a significantly (P less than 0.001) shorter platelet MLS than calculations using whole blood samples. It is concluded that both 51Cr and 111In are acceptable as radiolabels for both fresh and stored platelets. However, it appears that the viability of stored platelets may be influenced by the choice of label, and caution must be taken when these isotopes are used together in dual tracer experiments. Also, our results show that a meticulously standardized processing of blood samples and experimental data is required to enable interlaboratory comparisons of the results.

Adult↗
PubMed1991

Leukocyte removal filtration of platelet concentrates. A study of platelet loss using 111In-labelled platelets and dynamic gamma camera scintigraphy.

111In labelled platelets and gamma camera scintigraphy were used for the study of the platelet loss during leukocyte removal filtration of stored platelets. Two different filters were examined, Imugard IG500 and Pall PL100, and platelet pools containing varying number of platelet concentrates were filtered. It was found that a sizeable amount of the platelets was trapped within the filter. Some of the trapped platelets could be recovered by rinsing the filters with normal saline. The most appropriate rinsing volume to recover lost platelets seemed to match with the "dead space" volume within the filter. It is concluded that radiolabelled platelets and gamma camera scintigraphy appears to be an excellent method to investigate the dynamic events of platelet loss during leukocyte removal filtration. This technique should be well applicable for the study of technological advances in filter construction.

Blood Platelets↗